{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:36:34Z","timestamp":1776926194530,"version":"3.51.2"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Renal fibrosis (RF) is a refractory disease characterized by excessive deposition of extracellular matrix, leading to tissue damage and scar formation.\n                      <jats:italic>Fructus arctii<\/jats:italic>\n                      (the dried ripe fruit of\n                      <jats:italic>Arctium lappa<\/jats:italic>\n                      L.) is a typical medicinal and edible plant widely utilized in both traditional medicine and culinary practices, rich in lignans, phenolic acids, and dietary fibers. Studies have shown that arctigenin (ATG), the main active component of\n                      <jats:italic>F. arctii<\/jats:italic>\n                      , possesses pharmacological effects including anti-inflammatory, anti-fibrotic, and anti-oxidative stress properties. However, the mechanism by which ATG ameliorates RF remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An\n                      <jats:italic>in vivo<\/jats:italic>\n                      unilateral ureteral obstruction (UUO) rat model of RF and an\n                      <jats:italic>in vitro<\/jats:italic>\n                      TGF-\u03b21-induced HK-2 cell fibrosis model were established. The therapeutic effects of ATG were evaluated through pharmacodynamic experiments. Transcriptomics and proteomics were employed to screen and detect key genes, proteins, and mechanisms involved in ATG-mediated improvement of RF. Finally, core mechanisms were validated both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      using experiments such as RT-qPCR, Western blot, immunofluorescence, and flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      , ATG improved renal function, alleviated pathological damage, and reduced fibrosis. Combined transcriptomic and proteomic analyses revealed enrichment of pathways related to S100A8\/A9, the NF-\u03baB signaling axis, the TCA cycle, and oxidative phosphorylation. Molecular docking demonstrated good binding affinity between ATG and key targets. Further\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      validation revealed that ATG downregulated the expression of key factors in the S100A8 signaling axis, ameliorated impairments in the TCA cycle and oxidative phosphorylation by inhibiting NF-\u03baB phosphorylation, consequently suppressed the expression of inflammatory and oxidative stress factors, and ultimately downregulated the levels of fibrotic factors by inhibiting the epithelial-mesenchymal transition (EMT) process, thereby improving RF. Using paquinimod, a specific S100A8\/A9 inhibitor, we further demonstrated that pharmacological blockade of this pathway recapitulated the anti-fibrotic effects of ATG, providing causal evidence for its functional relevance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ATG exhibits therapeutic effects in ameliorating RF. Its mechanism involves regulating the TCA cycle and oxidative phosphorylation impairments via the S100A8\/A9\/NOX\/NF-\u03baB signaling pathway, thereby inhibiting inflammation and oxidative stress-driven EMT to improve RF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1796732","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:37:22Z","timestamp":1776922642000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elucidating the therapeutic efficacy and mechanisms of arctigenin in ameliorating renal fibrosis: a combined transcriptomic and proteomic study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yufei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiduo","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longshan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]},{"name":"Department of Pharmacy, Shenyang Pharmaceutical University","place":["Benxi, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukun","family":"Bo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Academic Affairs, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Hospital of Baotou","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Fourth Hospital of Baotou","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guodong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"An","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Baotou Medical College","place":["Baotou, Inner Mongolia Autonomous Region, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/s41581-025-00934-5","article-title":"Advances and challenges in kidney fibrosis therapeutics","volume":"21","author":"Abbad","year":"2025","journal-title":"Nat. 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